rs148424397

Variant names:

• chr6-31883395-G-A
• rs148424397
• NM_006709.5:c.2961C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_006709.5(EHMT2):​c.2961C>T​(p.Cys987Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,612,886 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (12 hom.)
• Consequence: EHMT2 NM_006709.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.220
• Publications: 2 publications found

Genes affected

EHMT2 (HGNC:14129): (euchromatic histone lysine methyltransferase 2) This gene encodes a methyltransferase that methylates lysine residues of histone H3. Methylation of H3 at lysine 9 by this protein results in recruitment of additional epigenetic regulators and repression of transcription. This gene was initially thought to be two different genes, NG36 and G9a, adjacent to each other in the HLA locus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

EHMT2-AS1 (HGNC:39751): (EHMT2 and SLC44A4 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 6-31883395-G-A is Benign according to our data. Variant chr6-31883395-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2656431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.22 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006709.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2	NM_006709.5	MANE Select	c.2961C>T	p.Cys987Cys	synonymous	Exon 23 of 28	NP_006700.3
	EHMT2	NM_001363689.2		c.3132C>T	p.Cys1044Cys	synonymous	Exon 22 of 27	NP_001350618.1	A2ABF9
	EHMT2	NM_001289413.2		c.3030C>T	p.Cys1010Cys	synonymous	Exon 21 of 26	NP_001276342.1	A2ABF8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EHMT2	ENST00000375537.9	TSL:1 MANE Select	c.2961C>T	p.Cys987Cys	synonymous	Exon 23 of 28	ENSP00000364687.4	Q96KQ7-1
	EHMT2	ENST00000395728.7	TSL:1	c.3132C>T	p.Cys1044Cys	synonymous	Exon 22 of 27	ENSP00000379078.3	A2ABF9
	EHMT2	ENST00000962959.1		c.2961C>T	p.Cys987Cys	synonymous	Exon 23 of 29	ENSP00000633018.1

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 191 AN: 152188 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00225

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000869 AC: 213 AN: 245194 AF XY: 0.000822

Gnomad AFR exome AF: 0.000133

Gnomad AMR exome AF: 0.00128

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000470

Gnomad NFE exome AF: 0.00134

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00124 AC: 1808 AN: 1460580 Hom.: 12 Cov.: 32 AF XY: 0.00124 AC XY: 902 AN XY: 726588

African (AFR) AF: 0.000119 AC: 4 AN: 33474

American (AMR) AF: 0.00139 AC: 62 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86214

European-Finnish (FIN) AF: 0.000535 AC: 28 AN: 52306

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.00150 AC: 1663 AN: 1111928

Other (OTH) AF: 0.000795 AC: 48 AN: 60376

GnomAD4 genome AF: 0.00125 AC: 191 AN: 152306 Hom.: 1 Cov.: 32 AF XY: 0.00111 AC XY: 83 AN XY: 74474

African (AFR) AF: 0.0000481 AC: 2 AN: 41558

American (AMR) AF: 0.00183 AC: 28 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00225 AC: 153 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00133 Hom.: 0

Bravo AF: 0.000839

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00131

EpiControl AF: 0.000593

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.6
DANN	Benign	0.87
PhyloP100		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148424397; hg19: chr6-31851172;